Induction of pituitary cytokine transcripts by peripheral lipopolysaccharide

Systemically administered lipopolysaccharide (LPS) elicits profound changes in pituitary hormone secretion. Pro-inflammatory cytokines have been propo sed as mediators of these responses. In this study, we used in-situ hybridi zation histochemistry to investigate LPS-induced cytokine gene expression i n the rat pituitary. After i.p. or i.v. injection of various doses of LPS, mRNA for the immediate-early gene I kappa Bu tan inhibitor of NF-kappa B, a transcription factor that regulates the expression of many pro-inflammator y cytokines) was induced in the anterior lobe as early as 0.5 h. The induce d I kappa B alpha mRNA expression peaked at 1 h. In the posterior lobe, I k appa B alpha mRNA was first induced at 0.5 h and peaked at 2 h. A similar s patiotemporal pattern of interleukin-1b (IL-1) mRNA induction was observed. In addition, at 2 h after injection, TNF alpha, IL-1 beta converting enzym e (ICE), and IL-1 receptor antagonist (IL-1RA) mRNAs were induced in both a nterior and posterior robes. Type 1 IL-1 receptor(lL-1R1) mRNA was constitu tively expressed in the pituitary, and its expression level did not change after the LPS injection. Interestingly, the mRNA coding for glial fibrillar y acidic protein (GFAP), an astrocyte marker, was selectively induced in th e posterior lobe at 2 h after LPS injection, suggesting that LPS affects pi tuicyte function. Together, these results suggest that LPS acts directly on the pituitary to rapidly induce cytokine expression. Locally synthesized c ytokines may activate cytokine receptor bearing cells to modulate the endoc rine activities of the pituitary.